The Effect of Cage Shape on Nanoparticle-Based Drug Carriers: Anticancer Drug Release and Efficacy via Receptor Blockade Using Dextran-Coated Iron Oxide Nanocages

Abstract

Although a range of nanoparticles have been developed as drug delivery systems in cancer therapeutics, this approach faces several important challenges concerning nanocarrier circulation, clearance, and penetration. The impact of reducing nanoparticle size on penetration through leaky blood vessels around tumor microenvironments via enhanced permeability and retention (EPR) effect has been extensively examined. Recent research has also investigated the effect of nanoparticle shape on circulation and target binding affinity. However, how nanoparticle shape affects drug release and therapeutic efficacy has not been previously explored. Here, we compared the drug release and efficacy of iron oxide nanoparticles possessing either a cage shape (IO-NCage) or a solid spherical shape (IO-NSP). Riluzole cytotoxicity against metastatic cancer cells was enhanced three-fold with IO-NCage. The shape of nanoparticles (or nanocages) affected the drug release point and cellular internalization, which in turn influenced drug efficacy. Our study provides evidence that the shape of iron oxide nanoparticles has a significant impact on drug release and efficacy.

Nanoparticle‐Based Nanomedicines to Promote Cancer Immunotherapy: Recent Advances and Future Directions

“…More interestingly, cage‐structured iron oxide nanoparticles loading Riluzole, a cell membrane pathway inhibitor, increased the propensity of cytotoxicity to metastatic cancer cells in comparison with spherical one owing to the high payload and the membrane localization . They found that the more positively charged spherical nanoparticles are internalized in a shorter time than the nanocages with negative charges, thus the negatively charged nanocages more efficiently block the membrane pathway.…”

Nanocaged platforms: modification, drug delivery and nanotoxicity. Opening synthetic cages to release the tiger

“…For particles smaller than 100 nm, spherical shaped NPs show the highest cell uptake 91 . In a study, the effect of NC structures on localization of nanocarriers in and around the cells and their cellular uptake was investigated by Rampersaud et al 92 . Here, longer dwell-time of NPs at the outer membrane of cancer cells was a priority to effectively release the ion channel blocking agent.…”

“…This difference was proposed to be related to the charge-screening effect of NC surface. Riluzole inhibited the secretion of glutamate by cancer cells via blocking the sodium ion channels, leading to prevention of glutamate receptor activation, thus lowering cancer cell growth (Figure 3-a) 92 . Particle surface charge also plays a significant role in NP-cell interactions and cell uptake.…”

“…Taking the advantage of the EPR effect, more accumulation of NPs (and macromolecules) can be achieved, so-called as “passive” targeting, which has been investigated in different experimental studies of NCs. The interplay of cage-shaped NPs with EPR effect and cellular internalization in tumor tissues have been also investigated 9492 .…”

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“…Physicochemical features including size, shape, surface functionalization, and dispersion state of nanoparticles would all affect their performances . Gold nanocaps or semishells demonstrate novel plasmonic and optical properties due to the presence of unique cavities within gold nanoparticles .…”